tbuckley/cabot-search huggingface dataset:
ATRT-05. Infants and newborns with atypical teratoid/rhabdoid tumors (ATRT) and extracranial malignant rhabdoid tumors: a unique and challenging population
Authors: Karolina Nemes, Pascal D Johann, Mona Steinbügl, Miriam Gruhle, Susanne Bens, Denis Kachanov, Margarita Teleshova, Hauser Peter, Thorsten Simon, Stephan Tippelt, Wolfgang Eberl, Martin Chada, Vicente Santa-Maria Lopez, Lorenz Grigull, Pablo Hernáiz-Driever, Matthias Eyrich, Jane Pears, Till Milde, Harald Reinhard, Alfred Leipold, Marianne v de Wetering, Maria João Gil-da-Costa, Georg Ebetsberger-Dachs, Kornelius Kerl, Andreas Lemmer, Heidrun Boztug, Rhoikos Furtwängler, Uwe Kordes, Reiner Siebert, Christian Vokuhl, Martin Hasselblatt, Brigitte Bison, Thomas Kröncke, Patrick Melchior, Beate Timmermann, Joachim Gerss, Michael C Frühwald
Journal: Neuro-Oncology (2022)

Abstract INTRODUCTION: Malignant rhabdoid tumors (MRT) predominantly affect infants. Patients below six months represent a particularly challenging group: intensity of therapy is limited by toxicity to developing organs. Information on prognostic factors, toxicity and long term outcome is sparse. METHODS: Clinical, genetic, and treatment data of 100 patients (less than 6 months at diagnosis) from 13 European countries were analyzed (2005-2020). Tumors and matching blood samples were examined for SMARCB1 mutations using FISH, MLPA and Sanger sequencing. DNA-methylation subgroups (ATRT-TYR, ATRT-SHH, and ATRT-MYC) were determined using DNA methylation arrays. RESULTS: A total of 45 patients presented with ATRT, 29 with extracranial, extrarenal (eMRT) and 9 with renal rhabdoid tumors (RTK). Seventeen patients demonstrated synchronous tumors (SYN). Distant metastases at diagnosis (M+) were present in 27% (26/97). A germline mutation (GLM) was detected in 55% (47/86). Methylation subgroup status was available in 50% (31/62) of ATRT or SYN (SHH=13, TYR=13, MYC=4, SHH+TYR=1). The 5-year overall- (OS) and event free survival (EFS) rates were 23.5±4.6% and 19±4.1%, respectively. Male sex (11±5% vs. 35.8±7.4%), M+ (6.1±5.4% vs. 36.2±7.4%), presence of SYN (7.1±6.9% vs. 26.6±5.3%) and -GLM (7.7±4.2% vs. 45.7±8.6%) were significant prognosticators of 5-year OS, in univariate analysis. Molecular subgroup and survival analyses confirmed the previously described survival advantage of ATRT-TYR. In an adjusted multivariate model clinical factors that influence prognosis were: male sex [HR: 2.1 (1.2 – 3.6)], M+ [3.3 (1.8 – 6)], GLM [HR: 2 (1.1 – 3.6)] and maintenance therapy [HR: 0.3 (0.1 – 0.8)]. CONCLUSION: In this large cohort of homogenously treated infants with MRT, significant predictors of outcome were sex, M+, GLM and maintenance therapy. We confirm the need to stratify which patient group benefits from multimodal treatment, and which patients need novel therapeutic strategies. Biomarker-driven tailored trials may be a key option.
Variation in survival rates among patients with angiosarcoma based on demographic and socioeconomic factors in academic versus non-academic settings: An NCDB analysis.
Authors: Zachary Creech, Gia Thinh Truong, Regan Denny, Robert W. Hu, Kiana Verplancke, Sarah J Aurit, Peter T. Silberstein
Journal: Journal of Clinical Oncology (2022)

e23537 Background: Angiosarcomas are malignancies of endothelial-cell origin representing 2% of soft-tissue sarcomas. Although the number of cases of angiosarcoma continues to rise, the prognosis is generally poor and treatment options remain limited. Due to the rarity of angiosarcoma and limited available literature, this study is intended to analyze the impact of demographic and socioeconomic factors on patients’ survival rates in academic versus non-academic settings. Methods: We performed a retrospective analysis of 5,544 patients diagnosed with angiosarcoma from the National Cancer Database (NCDB) between 2004-2017. Patients were stratified by facility type and compared via Kaplan-Meier analysis, log-rank test, chi-square analyses, and ANOVA. Additionally, a cox proportional hazards multivariate regression model was used. The following demographic factors were examined: age, sex, reported race and ethnicity, mean survival rates utilizing the Charlson Comorbidity Index, facility type where patients received treatments, and treatment modalities. Furthermore, the assumption of proportionality was tested for each variable. Data was analyzed using Statistical Analysis Software (SAS). Results: Higher rates of death were seen in those of male sex, African American race, increased age (&gt; 72), and increasing Charlson-Deyo scores. There was an increased risk of death for older African American males with non-zero Charlson-Deyo scores. Additionally, patients from areas of increased income had decreased rates of death. After adjusting for most variables, patients who were treated at academic facilities had an 8.5% decreased risk of death compared with patients treated at non-academic facilities (95% CI: 1.5% to 15.0%; P = 0.019). Conclusions: Our study results indicate that certain demographic and socioeconomic factors may be linked to poorer survival outcomes in patients with angiosarcoma. Further investigation of socioeconomic barriers and prognostic factors for angiosarcoma may help to identify populations at risk for poor treatment outcomes and guide disease management.
LINC-11. Intrathecal methotrexate in a young child with medulloblastoma with extensive nodularity. An alternative to intra-ventricular route in Low and Middle Income Countries?
Authors: Carlos Leal-Cavazos, Jose Arenas-Ruiz, Oscar Vidal-Gutierrez
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND: In places where determination of molecular subgrouping of Medulloblastoma is not available, histology remains standard for risk stratification and treatment. Young children with medulloblastoma treated with craniospinal irradiation show a negative impact in neurocognitive functions, thus avoiding radiation in this specific population is encouraged. High dose chemotherapy and stem cell rescue have been internationally used as a strategy to spare radiation in infants and young children with Medulloblastoma. German HIT protocol (SKK) reported a PFS 85±8 % and good cognitive outcome in patients with Desmoplastic Medulloblastoma treated with intra-ventricular (i.vtr.) methotrexate (MTX). SKK protocol includes 36 i.vtr. administrations of MTX through a subcutaneous reservoir. Complications related to the use of this kind of reservoir could be due to the lack of experienced staff. METHODS: We report a patient with localized Medulloblastoma with extensive nodullarity (MBEN) treated as per SKK using intrathecal route instead of i.vtr MTX. A 2.5 year old boy was diagnosed with MBEN, surgery was complete and no shunt was required. Spinal MRI and CSF cytology were negative. Patient received 3 cycles of SKK protocol and 2 cycles of modified SKK. During the first 3 cycles he received one dose of intrathecal MTX 8mg on weeks 1, 3, 5 and 7 (12 doses in all). Patient remains free of disease 2 years after chemotherapy completion and without signs of leukoencephalopathy on T2 weighted cranial MRI. DISCUSSION: Intrathecal administration of MTX is commonly used for the treatment of Acute Lymphoblastic Leukemia, the most common childhood cancer. Staff in Low and Middle Income Countries (LMIC) may be better trained for such procedure than using a ventricular access device. This strategy could be considered when using SKK protocol in selected young children with Demoplastic Medulloblastoma and MBEN in LMIC where centers with enough experience with ventricular access device placement and handling are scarce.
Regorafenib (REGO) ± PD-1 inhibitor in second-line setting for unresectable hepatocellular carcinoma (uHCC) in real-world practice.
Authors: Huaqiang Bi, Jun Pei, Kuansheng Ma, Yanling Zhang, Feng Xia
Journal: Journal of Clinical Oncology (2022)

e16148 Background: No response and resistance occurred for the most uHCC patients with the treatment of molecular targeted agents and\or anti-PD-1 inhibitors. And the second-line therapies are still unmet the ideal clinical outcome. A pilot study that assessed the effectiveness of the combination therapy of REGO + PD-1 inhibitor in second-line setting for pts with advance uHCC showed promising result. Methods: This single-center, retrospective, real-world study was conducted between Jan 2019 to Jul 2021. All patients with uHCC, who were treated with second-line REGO + PD-1 inhibitor or REGO monotherapy were evaluated. The progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), overall survival (OS) were observed. Results: Forty-six patients with uHCC were included in the study, and most had received previous systemic treatment including targeted therapy and immunotherapy. In all pts, median treatment duration of regorafenib was 152.5 days. Median follow-up was 9.0 months. Tumor response was evaluated in 25 and 21 pts in REGO + PD-1 inhibitor and REGO monotherapy group respectively, ORR was 40% and 19.0% respectively; DCR was 88% and 71.4% respectively. Median OS was not reached in either group; the median PFS of the REGO + PD-1 inhibitor group was 11.5 months, which was significantly higher than that of the REGO monotherapy group (5.1 months) (C 2 =3.867; P=0.049). The most common AE grade ≥3 was diarrhea (4.3%), and was solely observed in REGO monotherapy group. Conclusions: Our preliminary findings suggested that the striking improvement in PFS and ORR were compelling in the REGO + PD-1 inhibitor group, and regardless of previous treatment, regorafenib was clinically effective for uHCC pts in second-line treatment whether in combination with PD-1 inhibitor or not in Chinese patients. And there was a trend to increased efficacy with no increased toxicity in combination therapy. Further analysis in a real-world study with a large sample size is crucial to substantiate our results.
A phase 2 multicenter, open-label, randomized, controlled trial in patients with stage II/III colorectal cancer who are ctDNA positive following resection to compare efficacy of autogene cevumeran versus watchful waiting.
Authors: Scott Kopetz, Van K. Morris, Vicente Alonso-Orduña, Pilar Garcia-Alfonso, Margarita Reboredo, Ana Fernandez Montes, Joan Maurel, David Paez, Anke C. Reinacher-Schick, Thomas Höhler, Javier Carrasco, Barbara Marie Galligan, Luisa Manning, Liane Preußner, Özlem Tureci, Ugur Sahin
Journal: Journal of Clinical Oncology (2022)

TPS3641 Background: Colorectal cancer (CRC) is one of the most commonly occurring cancers with high recurrence and mortality rate. Circulating tumor DNA (ctDNA) can be used as a marker of minimal residual disease after completion of surgical resection of stage II/III CRC, where detectable ctDNA levels (positive) post-AdCTx are associated with an increased risk of disease recurrence and novel therapies are needed. Autogene cevumeran is an investigational individualized neoantigen-specific immunotherapy that is designed to harness an immune response against patient-specific, tumor neoantigens. This clinical trial is in progress in patients with Stage II (high risk) / Stage III colorectal cancer who are ctDNA positive following resection. Methods: Autogene cevumeran is being evaluated in an open-label, Phase 2, randomized, controlled trial in patients with Stage II / III CRC patients who are ctDNA positive following resection. Patients are randomized to adjuvant therapy followed by autogene cevumeran compared to adjuvant therapy followed by watchful waiting. The primary endpoint is disease-free survival (DFS). The trial has a Biomarker Cohort of 15 patients who will receive autogene cevumeran irrespective of the ctDNA status to pursue exploratory objectives. The main study of the phase 2 trial consists of a randomized (1:1) design comparing the experimental arm (autogene cevumeran) with the observational arm (watchful waiting) in ctDNA positive CRC patients. A third Exploratory Cohort explores the efficacy and safety of autogene cevumeran in ctDNA positive CRC patients with early recurrence/relapse during or after completion of AdCTx. Patients enrolled onto the experimental group, the biomarker and exploratory cohorts will receive autogene cevumeran 6x q1w, followed by 2x q2w, followed by 7 “booster” doses q6w, to receive a total of 15 doses (dosed at 25μg). AEs are assessed according to CTCAE v5. DFS will be determined by an independent central radiology assessment. Key eligibility criteria include 1) Patients must have stage II/III rectal cancer or stage II (high risk)/III colon cancer that has been surgically resected (R0 confirmed by pathology report); 2) patients must be ctDNA positive following resection; and 3) at least 5 tumor neoantigens must be identified in the provided tumor sample for autogene cevumeran manufacturing (RNA lipoplex, RNA-LPX). ClinicalTrials.gov identifier: NCT04486378.
Anterior colporrhaphy and sacrospinous hysteropexy in women with pelvic organ prolapse: Urodynamic findings and functional outcomes
Authors: R. Balsamo, F. Uricchio, E. Costantini, E. Illiano, M. De Sio, D. Arcaniolo, M. Trivellato, S. Domizio, R. Ranavolo, F. Di Fiore, A. D'Afiero
Journal: European Urology (2022)
RONC-10. Radiation-induced hypothyroidism in pediatric brain tumour survivors: radiation dose-volume predictors of its onset
Authors: Camilla Satragno, Antonio Verrico, Flavio Giannelli, Sucheeta Campora, Marianna Turazzi, Luca Carmisciano, Francesca Cavagnetto, Natascia Di Iorgi, Marco Crocco, Gianluca Piccolo, Emilio Casalini, Claudia Milanaccio, Maria Luisa Garrè, Liliana Belgioia, Salvina Barra
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND: Central hypothyroidism is a well-known late effect of radiotherapy in children treated for brain tumours. AIM: To determine the risk of central hypothyroidism (CH) and the radiation dose-volume predictors of its onset. METHODS: We retrospectively analyzed 64 patients who received radiotherapy for brain tumours, with at least a 2-year-long serological follow-up, determined CH incidence and radiation predictive factors of its onset. To estimate the risk of CH according to the site of the tumour inside the central nervous system (CNS) we considered the sellar-suprasellar region, anterior cranial region, and others. For the same purpose, a further analysis was conducted comparing craniospinal radiotherapy (CSI) versus involved-field radiotherapy (IF-RT). Dose constraints for CH were determined using the Receiver Operating Characteristic to identify the pituitary mean dose cut-off and the probability of CH over time was assessed with the Cox model. RESULTS: 18 cases were excluded due to the presence of CH before RT; 17 of remaining 46 (37%) patients presented CH during follow-up: 14 of 17 (82%) patients received CSI, 3 (18%) IF-RT sellar-suprasellar region and anterior cranial region. A median dose higher than 30.5 Gy to the pituitary gland results in a 4-fold increased risk of central hypothyroidism (HR=3.9; 95% CI 1.1, 13.4; p=0.03). Almost 90% of events occurred within 5 years after treatment ended. 29 of 46 (63%) patients did not manifest CH and were in the "other regions”. However, 14 of these (48%) underwent CSI. CONCLUSIONS: Our data confirm the relationship between central hypothyroidism and mean pituitary radiation dose, and suggest a minimum of 5 years follow up in children brain tumor survivors. Tumours outside the sellar-suprasellar region, treated with radiotherapy, are not associated with CH onset. A significant association between CSI and risk of CH, highlighted with our analysis, warrants further investigations and a longer follow up
Surgical and oncological outcomes of post chemotherapy laparoscopic retroperitoneal lymph node dissection in stage IIA-III non seminomatous germ-cell tumors
Authors: S. Nazzani, M. Catanzaro, D. Biasoni, A. Macchi, S. Stagni, T. Torelli, A. Tesone, P. Giannatempo, E. Agostini, M. Colecchia, L. Cattaneo, L. Piva, R. Salvioni, N. Nicolai
Journal: European Urology (2022)
Crowdsourcing of artificial intelligence algorithms for diagnosis and Gleason grading of prostate cancer in biopsies
Authors: K. Kartasalo, W. Bulten, P-H.C. Chen, P. Ström, H. Pinckaers, K. Nagpal, P. Ruusuvuori, G. Litjens, M. Eklund
Journal: European Urology (2022)
Prevalence and risk factors for hepatitis E virus infection in blood donors: a nationwide survey in Italy, 2017 to 2019
Authors: Enea Spada, Matteo Simeoni, Antonio Martina, Ilaria Pati, Umbertina Villano, Daniela Adriani, Agnese D’Angiò, Elena Tritarelli, Stefania Taffon, Stefania Bellino, Stefano Boros, Roberta Urciuoli, Francesca Masiello, Giuseppe Marano, Roberto Bruni, Patrizio Pezzotti, Anna Rita Ciccaglione, Simonetta Pupella, Vincenzo De Angelis, Giulio Pisani
Journal: Eurosurveillance (2022)

BackgroundIn high-income countries, hepatitis E virus (HEV) infection is mainly a zoonosis. However, it is also transfusion-transmissible and some countries, but not Italy, have introduced HEV screening for blood donations.AimWe assessed HEV infection prevalence and risk factors in a nationwide sample of Italian blood donors.MethodsWe selected 107 blood establishments (BE) distributed in the 20 Italian regions by a stratified two-stage design and invited them to participate in the study. Donors were tested for anti-HEV IgG and IgM and HEV RNA. Sociodemographic data and risk factors were collected through a questionnaire.ResultsOverall, 60 BE from 60 provinces in 19 Italian regions joined the study. We assessed HEV markers in 7,172 blood donors, of whom 6,235 completed the questionnaire. Overall crude and adjusted anti-HEV IgG prevalences were 8.3% and 5.5%, respectively. Overall anti-HEV IgM prevalence was 0.5%, while no blood donor was HEV RNA-positive. Anti-HEV IgG prevalence varied widely among regions (range: 1.3%-27.20%) and hyperendemic prevalences (> 40%) were detected in some provinces in two regions. Older age (AOR = 1.81; 95% CI: 1.36-2.41), foreign nationality (AOR = 2.77; 95% CI: 1.06-7.24), eating raw pork liver sausages (AOR = 2.23; 95% CI: 1.55-3.20) and raw homemade sausages (AOR = 3.63; 95% CI: 2.50-5.24) were independent infection predictors.ConclusionItalian blood donors showed a low to moderate HEV seroprevalence. High levels in some regions and/or provinces were mainly attributable to eating habits. Prevention should include avoiding consumption of raw or undercooked meat and safe production of commercial pork products.
Investigating the impact of NGS data availability on clinical decision-making in brain cancer.
Authors: Adam Eckburg, Jordan John, Priya Kumthekar
Journal: Journal of Clinical Oncology (2022)

2032 Background: Next-generation sequencing (NGS) of cancer specimens is a valuable diagnostic tool that can provide detailed information regarding specific somatic genetic alterations within a tumor with potential for targeted treatment. Despite the increasing availability of NGS, preliminary data by John et al. from ASCO 2021 suggested that clinical decision making is not frequently impacted by NGS results in the setting of glioblastoma. Herein, we report how NGS data impacts other primary tumor types, including astrocytoma, oligodendroglioma, and various rare subtypes. Methods: A retrospective chart review was performed to assess the proportion of brain cancer patients receiving targeted treatment instead of standard therapeutics after NGS sequencing. Pertinent medical information was ascertained from Epic and the Electronic Data Warehouse. Targeted treatments were defined as those recommended by the Tempus report for NGS-identified potentially actionable mutations. Patients were stratified into one of three categories: astrocytoma, oligodendroglioma, or other rare subtypes (including meningioma, ependymoma, ganglioma, pleomorphic xanthoastrocytoma, atypical teratoid rhabdoid tumors, glioneuronal tumors, and CNS lymphomas). Results: Of 44 Astrocytoma patients with potentially actionable mutations, four (9.1%) were treated with targeted therapy in the form of Enasidenib, ONC201, Nivolumab, and Depatuxizumab, while 40 received NGS agnostic treatment. In 37 Oligodendroglioma patients, three (8.1%) were treated with either targeted Vorasidenib or Ivosidenib, while 34 were started on NGS agnostic therapies. Lastly, four (10.0%) of 40 patients with other rare primary tumor types received either Ibrutinib, Dabrafenib+Trametinib, Vigabatrin, or Vemurafenib as targeted therapy. Avastin and/or standard Temozolomide chemotherapy were the most common NGS agnostic therapies employed by clinicians across all three subclasses. Conclusions: Although a substantial number of potentially actionable mutations were detected by NGS, the presence of this data paired with Tempus targeted recommendations rarely impacted clinician decision-making, ranging from 8.1-10.0% of the time. Despite the availability of resources to prescribe targeted treatment, providers consistently chose NGS agnostic therapies instead. Utilization of targeted treatment may become more frequent over time, as more novel agents come to market and their efficacy is further elucidated.
Cambrelizumab plus chemotherapy as conversion therapy for unresectable metastatic gastric cancer: A single-arm, multicenter, prospective clinical trial.
Authors: Shuang Li, Liang He, Meng Li, Quan Wang
Journal: Journal of Clinical Oncology (2022)

e16032 Background: Although anti-PD-1 antibody in combination with chemotherapy has shown promising antitumor activity in advanced gastric or gastroesophageal junction adenocarcinoma (GC/GEJC), the evidence of conversion therapy for initially unresectable GC/GEJC is limited. Camrelizumab combined chemotherapy as conversion therapy for unresectable GC/GEJC was a prospective, single-arm, phase 2 study we conducted. Here, we updated the results of efficacy and safety of this study. Methods: Patients with HER-2 negative and PD-L1+ (CPS≥1) or MSI-H/dMMR, or EBV (+) unresectable gastric cancer were enrolled. Eligible patients must meet one of the following criteria: 1) peritoneal metastasis (CY1P0 or P1a, P1b or PCI &lt; = 10); 2) liver metastasis (H1), &lt; 3 metastatic sites; 3) para-aortic lymph node metastasis. For patients with lymph node metastasis or liver metastasis, they received 6 cycles of camrelizumab (200mg ivgtt on day1, q3w) plus SOX (Oxaliplatin, 130mg/m² ivgtt, d1, q3w, S-1 40/50/60 mg based on BSA, po, bid, d1-14, q3w) as conversion therapy. For patients with peritoneal metastasis, they received 6 cycles of camrelizumab (200mg ivgtt on day1, q3w) plus IP (Paclitaxel, 50mg/m², ivgtt, d1, d8, q3w. Paclitaxel, 20mg/m², intraperitoneal administration, d1, d8, q3w. S-1 40/50/60 mg based on BSA, po, bid, d1-14, q3w) as conversion therapy. Then patients without disease progression evaluated by imaging underwent gastrectomy of D2 lymph node dissection. The primary endpoint was R0 resection rate and 2 years survival rate, the secondary endpoints were objective response rate (ORR), pathological complete response (pCR) rate and overall survival. Results: Between December 30, 2020 and January 5, 2022, 31 patients were enrolled. 19 patients received SOX plus camrelizumab, 12 patients received IP plus camrelizumab. Unfortunately, 7 of them were confirmed PD by imaging. In addition, two patients refused gastrectomy and withdrew from the study. 12 patients underwent gastrectomy and 8 patients are in the process of conversion therapy. Among the 12 patients were evaluable, 9 of them gained R0 resection (75%), 1 patient (8.3%) achieved pCR and 2 patient (16.6%) reached TRG1. The most common grade 3 adverse events (AEs) were neutropenia (27.6%). No serious AEs resulted in termination of treatment or death. Conclusions: Camrelizumab combined with chemotherapy was an effective and safe conversion therapy strategy for patients with unresectable GC/GEJC. Furthermore, the analysis of biomarkers with clinical benefits is undergoing. Clinical trial information: NCT04694183.